Koninklijke Lierse Sportkring was first established in 1906 after a meeting in a local pub. Commonly called Lierse, the club has enjoyed significant success at domestic level, despite struggling to maintain their status as a top division team. Lierse are owned by Egyptian businessman Maged Samy and, as a result, have an affliliation with one of his other teams, Wadi Degla.

Lierse made their first appearance in the top flight in the 1927-28 season and prior to the outbreak of World War II, emerged as one of the country's major teams. In 1931–32 they were crowned as Belgian champions for the first time, before finishing as runners up in 1934–35 and 1938–39. They won the title again in 1940–41, although this was not considered an official season due to the war. In 1941–42, however, they did win their second official First Division title.

In the post-war years, Lierse have been relegated from the First Division multiple times, but their spells in the top flight have been laced with major honours along the way. In 1959–60 they added their third official league championship to their trophy haul, while in 1968–69, they lifted the Belgian Cup for the first time. The 1996–97 season saw the club win their fourth league title and two years later, they won their second Belgian Cup.

Bernard Voorhoof is perhaps the most successful player to have played for Lierse. The legendary striker scored 350 goals for the club and was named the team's 'Player of the Century' in 2006. Other notable former players include Jan Ceulemans and Tomasz Radzinski, while Romelu Lukaku is a product of the team's youth academy.

The side play home matches at the Herman Vanderpoortenstadion. The stadium is named after a prominent politician from the area and is currently able to hold up to 14,538 spectators.